公开(公告)号：WO2023091553A1

公开(公告)日：2023-05-25

申请号：PCT/US2022/050218

申请日：2022-11-17

申请人： SERMONIX PHARMACEUTICALS, INC.

发明人： KOMM, Barry, Samuel ,  GREENE, Geoffrey, L.

IPC分类号： A61K31/40 ,  A61K31/4155 ,  A61K31/4196 ,  A61K31/506 ,  A61K31/519 ,  A61K31/5685 ,  A61K45/06 ,  A61P35/00 ,  G01N33/574

摘要： The disclosure provides an effective amount of lasofoxifene, or a pharmaceutically acceptable salt or functional derivative thereof, for use in methods for treating estrogen receptor positive (ER+) cancer in a patient who has progressed on an aromatase inhibitor. Of particular interest are ER+ cancers that do not harbor a gain of function missense mutation within the ligand binding domain (LBD) of the Estrogen Receptor 1 (ESRI) gene.

公开(公告)号：WO2021113219A1

公开(公告)日：2021-06-10

申请号：PCT/US2020/062673

申请日：2020-12-01

申请人： GENENTECH, INC.

发明人： LAUCHLE, Jennifer O'Hara ,  MAMOUNAS, Michael Joseph ,  SCHUTZMAN, Jennifer Lee ,  FRIEDMAN, Lori Sickels ,  HUANG, Jian

IPC分类号： A61K31/41 ,  A61K31/519 ,  A61K31/553 ,  A61K31/5685 ,  A61P35/00

摘要： Provided are combination therapies comprising a PI3K inhibitor (e.g., inavolisib), a CDK4/6 inhibitor (e.g., palbociclib), and fulvestrant; and methods of treating hormone receptor positive and HER2 negative (HR+/HER2-) locally advanced or metastatic breast cancer in a patient (preferably a patient with a PIC3CA mutant patient) comprising administering a therapeutically effective amount of inavolisib, or a pharmaceutically acceptable salt thereof, a CDK4/6 inhibitor (e.g., palbociclib), and fulvestrant or letrozole.

公开(公告)号：WO2021046374A2

公开(公告)日：2021-03-11

申请号：PCT/US2020/049442

申请日：2020-09-04

申请人： QUICKSILVER SCIENTIFIC, INC.

发明人： SHADE, Christopher W. ,  TIEU, Steven

IPC分类号： B82Y5/00 ,  A61K31/568 ,  A61K31/5685 ,  A61K9/00

摘要： Microemulsions are described where hydrophobic liquid droplets are distributed in a continuous hydrophilic liquid phase. The described microemulsions may be thought of as modified oil-in-water (MOIW) microemulsions, where both the "oil" and "water" phases of the microemulsion are modified. The oil phase droplets of the MOIW microemulsion are modified with alcohol and can solubilize alcohol-soluble species, including nonderivatized hormones. The polar continuous "water" phase of the MOIW microemulsion is modified with a sugar or sugar alcohol.

公开(公告)号：WO2019236677A1

公开(公告)日：2019-12-12

申请号：PCT/US2019/035537

申请日：2019-06-05

申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  CROSBIE, Rachelle, H. ,  SHU, Cynthia

发明人： CROSBIE, Rachelle, H. ,  SHU, Cynthia

IPC分类号： A61K31/429 ,  A61K31/522 ,  A61K31/525 ,  A61K31/538 ,  A61K31/404 ,  A61K31/137 ,  A61K31/7076 ,  A61K31/40 ,  A61K31/5685 ,  A61K31/4422

摘要： Provided herein are methods for treating and preventing a disease related to diminution or dysfunction of a dystrophin-related complex in a subject in need thereof, comprising administering to the subject a compound that increases sarcospan. Also provided herein are pharmaceutical compositions comprising a compound that increases sarcospan, or a pharmaceutically acceptable salt or ester thereof, useful for the treatments described herein.

公开(公告)号：WO2016146591A1

公开(公告)日：2016-09-22

申请号：PCT/EP2016/055467

申请日：2016-03-14

申请人： ASTRAZENECA AB

发明人： GREEN, Stephen ,  YELLAND, Ursula, Joy ,  HUDSON, Kevin

IPC分类号： A61K45/06 ,  A61K31/138 ,  A61K31/40 ,  A61K31/4196 ,  A61K31/437 ,  A61K31/4535 ,  A61K31/497 ,  A61K31/506 ,  A61K31/519 ,  A61K31/55 ,  A61K31/565 ,  A61K31/5685 ,  A61P35/00 ,  A61P35/02 ,  A61P35/04

CPC分类号： A61K31/497 ,  A61K31/138 ,  A61K31/40 ,  A61K31/4196 ,  A61K31/437 ,  A61K31/4535 ,  A61K31/506 ,  A61K31/519 ,  A61K31/55 ,  A61K31/565 ,  A61K31/5685 ,  A61K45/06 ,  A61K2300/00

摘要： The present specification relates to the use of combinations comprising 1-(4-(5-(5- amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3- yl)piperidin-1-yl)-3-hydroxypropan-1-one (Compound [I]) or a pharmaceutically acceptable salt thereof, and either a cyclin-dependent kinase (CDK) inhibitor or an anti- estrogen agent, or both a CDK inhibitor and an anti-estrogen agent, in the treatment or prophylaxis of cancer; pharmaceutical compositions comprising Compound [I] or a pharmaceutically acceptable salt thereof and either or both of a CDK inhibitor and an anti- estrogen agent; kits comprising Compound [I] or a pharmaceutically acceptable salt thereof and either or both of a CDK inhibitor and an anti-estrogen agent, optionally with instructions for use; methods of treatment comprising the simultaneous, sequential or separate administration of Compound [I] or a pharmaceutically acceptable salt thereof and either or both of a CDK inhibitor and an anti-estrogen agent, to a warm-blooded animal, such as man; and the intermittent dosing of Compound [I] or a pharmaceutically acceptable salt thereof either alone or in combination with either or both of a CDK inhibitor and an anti-estrogen agent.

摘要翻译： 本说明书涉及包含1-（4-（5-（5-氨基-6-（5-叔丁基-1,3,4-恶二唑-2-基）吡嗪-2-基） -1-乙基-1H-1,2,4-三唑-3-基）哌啶-1-基）-3-羟基丙-1-酮（化合物[I]）或其药学上可接受的盐，以及细胞周期蛋白 依赖性激酶（CDK）抑制剂或抗雌激素剂，或CDK抑制剂和抗雌激素剂两者均用于治疗或预防癌症; 包含化合物[I]或其药学上可接受的盐和CDK抑制剂和抗雌激素剂中的任一种或两者的药物组合物; 包含化合物[I]或其药学上可接受的盐以及任选地使用说明书的CDK抑制剂和抗雌激素剂中的任一种或两者的试剂盒; 包括将化合物[I]或其药学上可接受的盐以及CDK抑制剂和抗雌激素剂中的任一种或两者同时，顺序或分开施用于温血动物如人的治疗方法; 以及化合物[I]或其药学上可接受的盐单独或与CDK抑制剂和抗雌激素剂中的任一种或两者组合的间歇给药。

公开(公告)号：WO2016083325A1

公开(公告)日：2016-06-02

申请号：PCT/EP2015/077401

申请日：2015-11-24

申请人： FAERGEMANN, Jan ,  JOHANNSSON, Gudmundur ,  OHLSSON, Claes ,  BATCHELLER, Derek Gregory ,  JOHNSSON, Jörgen ,  TÖRNELL, Jan

发明人： FAERGEMANN, Jan ,  JOHANNSSON, Gudmundur ,  OHLSSON, Claes ,  BATCHELLER, Derek Gregory ,  JOHNSSON, Jörgen ,  TÖRNELL, Jan

IPC分类号： A61K31/192 ,  A61K31/5685 ,  A61P17/18 ,  A61P17/16 ,  A61P17/10 ,  A61P17/08 ,  A61P17/06 ,  A61P17/02 ,  A61P17/00

CPC分类号： A61K31/5685 ,  A61K8/06 ,  A61K8/062 ,  A61K8/365 ,  A61K8/63 ,  A61K9/0014 ,  A61K9/06 ,  A61K9/107 ,  A61K31/192 ,  A61K45/06 ,  A61P17/00 ,  A61P17/02 ,  A61P17/06 ,  A61P17/08 ,  A61P17/10 ,  A61P17/16 ,  A61P17/18 ,  A61Q19/00 ,  A61Q19/08 ,  A61K2300/00

摘要： The aim of the present study was to investigate the effect of a combination of triiodothyroacetic acid (TRIAC) and dehydroepiandrosterone (DHEA) compared with TRIAC, DHEA or placebo alone on corticosteroid induced effect on collagen synthesis in humans. Six healthy male human volunteers aged 40-65 participated. Four areas of abdominal skin were pre-treated for 3 weeks with betamethasone valerate cream. The same areas were then treated with one of the following alternatives in the same cream vehicle: TRIAC, DHEA, TRIAC+DHEA and placebo for 2 weeks. Then suction blisters were raised in each of these areas with a vacuum pump. The blister fluid from each area was collected and frozen until analysis. Analysis of amino terminal propeptide of human type I procollagen (PINP) in suction blister fluid was performed using a commercially available immunoassay (Orion Diagnostics) kit. This study has for the first time shown that a combination of TRIAC and DHEA could effectively stimulate collagen synthesis in skin pretreated with betamethasone valerate demonstrated by an increase in PINP, and that the combination was more effective than TRIAC or DHEA alone. This combination could be used to effectively treat skin atrophy in corticosteroid induced skin atrophy. It could also be used to treat skin atrophy due to other circumstances such as e. g. sun damaged skin and skin atrophy due to high age. Another interesting application would be to combine TRIAC and DHEA with a potent corticosteroid in order to prevent corticosteroid induced skin atrophy. If this combination still is effective in the treatment of eczema and psoriasis and without the risk of skin atrophy this combination will be a major breakthrough for the use of potent topical corticosteroids.

摘要翻译： 本研究的目的是调查三碘甲基乙酸（TRIAC）和脱氢表雄酮（DHEA）的组合与单独的TRIAC，DHEA或安慰剂组合对皮质类固醇诱导人类胶原合成的影响。 参加了六十岁的40-65岁健康男性志愿者。 用倍他米松戊酸酯霜预处理4个腹部皮肤区域3周。 然后在相同的奶油载体中使用以下替代物之一处理相同的区域：TRIAC，DHEA，TRIAC + DHEA和安慰剂2周。 然后用真空泵将这些区域中的每个区域吸起水泡。 收集每个区域的水泡液，冷冻至分析。 使用市售的免疫测定（Orion Diagnostics）试剂盒进行吸入泡状液中人I型前胶原（PINP）的氨基末端前肽的分析。 这项研究首次表明，TRIAC和DHEA的组合可以有效地刺激皮下预处理的皮肤胶原蛋白合成，通过PINP增加证明戊酸倍他米松，并且该组合比单独的TRIAC或DHEA更有效。 这种组合可用于有效治疗皮质类固醇诱导的皮肤萎缩中的皮肤萎缩。 它也可以用于治疗由于其他情况如e的皮肤萎缩。 G。 太阳损伤皮肤和皮肤萎缩由于年龄高。 另一个有趣的应用是将TRIAC和DHEA与强效皮质类固醇结合，以防止皮质类固醇诱导的皮肤萎缩。 如果这种组合在治疗湿疹和牛皮癣方面仍然有效，并且没有皮肤萎缩的风险，则这种组合将是使用强效局部皮质类固醇的重大突破。

公开(公告)号：WO2015135061A1

公开(公告)日：2015-09-17

申请号：PCT/CA2015/000142

申请日：2015-03-09

申请人： ENDORECHERCHE, INC.

发明人： LABRIE, Fernand ,  GAUTHIER, Sylvain

IPC分类号： A61K31/5685 ,  A61K31/352 ,  A61P5/26 ,  A61P5/32 ,  C07D311/60 ,  C07J1/00

CPC分类号： A61K31/5685 ,  A61K9/0019 ,  A61K9/0031 ,  A61K9/0053 ,  A61K31/453 ,  A61K38/24 ,  A61K45/06 ,  A61K2300/00

摘要： Novel methods for prevention, reduction or elimination of the incidence of male androgen deficiency symptoms or diseases including male hypogonadism-associated symptoms and diseases associated with low serum testosterone and/or low DHEA or low total androgens in susceptible warm-blooded animals including humans involving administration of an amount of a sex steroid precursor, particularly dehydroepiandrosterone (DHEA) and a selective estrogen receptor modulator (SERM) (particularly acolbifene), an antiestrogen or a prodrug of the two. The symptoms or diseases are loss of libido, erectile dysfunction, tiredness, loss of energy, depression, bone loss, muscle loss, muscle weakness, fat accumulation, memory loss, cognition loss, Alzheimer's disease, dementia, loss of body hair, fertility problems, insomnia, gynecomastia, anemia, hot flushes, sweats, decreased sense of well-being, obesity, osteoporosis, hypercholesterolemia, hyperlipidemia, atherosclerosis, hypertension, insulin resistance, cardiovascular disease and type 2 diabetes. Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.

摘要翻译： 用于预防，减少或消除男性雄激素缺乏症状或疾病的发生率的方法，包括男性性腺机能减退相关症状和与低血清睾酮和/或低DHEA或低总雄激素相关的疾病，包括涉及给药的易感温血动物 一类量的类固醇前体，特别是脱氢表雄酮（DHEA）和选择性雌激素受体调节剂（SERM）（尤其是阿曲比芬），二者的抗雌激素或前药。 症状或疾病是性欲丧失，勃起功能障碍，疲劳，能量损失，抑郁，骨丢失，肌肉损失，肌肉无力，脂肪堆积，记忆丧失，认知丧失，阿尔茨海默氏病，痴呆，身体毛发丧失，生育问题 ，失眠，男子女性发育不良，贫血，潮热，汗水，健康感，肥胖症，骨质疏松症，高胆固醇血症，高脂血症，动脉粥样硬化，高血压，胰岛素抵抗，心血管疾病和2型糖尿病。 还公开了用于递送本发明有用的活性成分和试剂盒的药物组合物。

公开(公告)号：WO2015033874A1

公开(公告)日：2015-03-12

申请号：PCT/JP2014/072790

申请日：2014-08-29

申请人： 大正製薬株式会社

发明人： 中尾　明子 ,  植田　康嗣 ,  槇原　史朗

IPC分类号： C12Q1/00 ,  A61K8/63 ,  A61K31/568 ,  A61K31/5685 ,  A61K38/22 ,  A61P17/14 ,  A61Q7/00 ,  G01N33/15

CPC分类号： A61K8/63 ,  A61K31/568 ,  A61K31/5685 ,  A61K38/09 ,  A61Q7/00 ,  G01N33/5088 ,  G01N33/743 ,  G01N2800/20

摘要： 　げっ歯類に男性ホルモンを投与する工程を含む、げっ歯類の毛周期における成長期から退行期への移行を促進する方法を提供する。さらには、げっ歯類において、（ａ）毛周期の休止期において、同調した成長期を誘導する工程、（ｂ）男性ホルモンを投与する工程、（ｃ）薬剤を投与する工程、及び（ｄ）男性ホルモン投与により促進されるげっ歯類の毛周期における成長期から退行期への移行が薬剤投与により抑制される程度を評価する工程、を含む薬剤の有効性を評価する方法を提供する。本発明により簡便なｉｎ　ｖｉｖｏ男性型脱毛症モデルにおいて、発毛剤、育毛剤等の有効性を効果的に評価が可能となる。

摘要翻译： 本发明提供了一种加速从啮齿动物的毛发循环的生长阶段转变到毛发周期的方法，该方法包括向啮齿动物施用睾丸激素的步骤。 还提供了一种用于评估啮齿动物药物功效的方法，所述方法包括（a）在毛发循环的后期阶段诱导同步成熟期的步骤，（b）施​​用睾酮的步骤，（c） 施用药物，以及（d）用于评估药物施用抑制由睾丸激素加速加速的啮齿动物的毛发周期中的从生长阶段转变为致癌相的程度的步骤。 通过本发明的简单的体内雄性型式秃发模型可以有效地评估毛发或毛发滋补剂的功效。

公开(公告)号：WO2014015416A9

公开(公告)日：2014-07-03

申请号：PCT/CA2013000654

申请日：2013-07-19

申请人： ENDORECH INC

发明人： LABRIE FERNAND

IPC分类号： A61K31/5685 ,  A61P15/00 ,  A61P15/02 ,  A61P15/12

CPC分类号： A61K31/5685 ,  A61K9/0034

摘要： Intravaginal DHEA is used for the treatment of at least one condition selected from the group consisting of female hypoactive sexual desire disorder, female sexual arousal disorder, female orgasm disorder and female sexual interest arousal disorder in a woman who either (1) is not suffering from symptoms of vulvo-vaginal atrophy and/or (2) is not suffering from moderate to severe dyspareunia.

摘要翻译： 阴道内DHEA用于治疗女性中至少一种选自雌性性欲抑制障碍，女性性唤起障碍，女性性高潮障碍和女性性兴趣性唤起障碍的病症，其中（1）不患有 外阴 - 阴道萎缩症状和/或（2）没有患中度至严重性交困难。

公开(公告)号：WO2013020215A1

公开(公告)日：2013-02-14

申请号：PCT/CA2012/000746

申请日：2012-08-09

申请人： ADAMS, Kenneth W.

发明人： ADAMS, Kenneth W.

IPC分类号： A61K31/4196 ,  A61K31/138 ,  A61K31/437 ,  A61K31/4453 ,  A61K31/451 ,  A61K31/5685 ,  A61K31/585 ,  A61P15/08 ,  A61P5/26

CPC分类号： A61K45/06 ,  A61K31/138 ,  A61K31/4196 ,  A61K31/437 ,  A61K31/4453 ,  A61K31/451 ,  A61K31/5685 ,  A61K31/585

摘要： The use of an aromatase blocker or an estrogen blocker is described in a method for increasing spermatogenesis and Seritolli cell function, and/or improving Leydig cell function, in order to to increase endogenous testosterone levels in a male mammal. The levels of active materials used are significantly lower than the levels of these materials used to treat female estrogen sensitive tumors.

摘要翻译： 在增加精子发生和Seritolli细胞功能和/或改善Leydig细胞功能的方法中描述了使用芳香酶抑制剂或雌激素阻断剂，以增加雄性哺乳动物的内源性睾酮水平。 使用的活性物质的水平显着低于用于治疗女性雌激素敏感性肿瘤的这些材料的水平。